US2008019968A1PendingUtilityA1
Detection, prevention and treatment of breast cancer
Est. expiryNov 19, 2024(expired)· nominal 20-yr term from priority
A61P 43/00G01N 33/5756G01N 33/57515
34
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Claims
Abstract
The invention provides compositions and arrays of glycans for detecting, treating and monitoring breast cancer in a human or other mammal.
Claims
exact text as granted — not AI-modified1 . An array of glycan molecules for detecting breast cancer in a patient test sample comprising a solid support and a library of glycan molecules, wherein at least one of the glycan molecules bind antibodies previously identified as being associated with neoplasia in patients with benign, pre-malignant or malignant breast tumors.
2 . The array of claim 1 , wherein the glycans are selected from the group consisting of ceruloplasmin, Neu5Gc(2-6)GalNAc, GM1, Sulfo-T, Globo-H, sialylated Tn (Neu5Ac-alpha6-GalNAc-alpha) and LNT-2.
3 . The array of claim 1 , wherein the glycans are selected from the group consisting of Tri-LacNAc, LacNAc-LeX-LeX, LacNAc-LacNAc, H-type-2-LacNAc, H-type2-LacNAc-LacNAc, GlcNAcβ3LacNAc, SLeXLacNAc, 3′SialylDiLacNAc, 3′Sialyl-tri-LacNAc, 6Sia-LacNAc-LeX-LeX and 6SiaLacNAc-LacNAc.
4 . The array of claim 1 , wherein each type of glycan in the library is attached to a solid support at a defined glycan probe location, wherein each glycan probe location defines a region of the solid support that has multiple copies of one type of similar glycan molecules attached thereto.
5 . The array of claim 1 , wherein the array is a microarray.
6 . The array of claim 1 , wherein the test sample is a bodily fluid.
7 . The array of claim 1 wherein the test sample is a blood sample, a serum sample, a plasma sample, a urine sample, a breast milk sample, a breast secretion sample, a nipple aspirate sample, an ascites fluid sample, a plural ascites fluid sample, a saliva sample, a cerebrospinal fluid sample, a vaginal secretion sample, an ovarian fluid sample or a tissue sample.
8 . The array of claim 1 , wherein the GM1 is Gal-beta3-GalNAc-beta-4-[Neu5Ac-alpha3]-Gal-beta-4-Glc-beta; wherein the Sulfo-T comprises Galβ3GalNAc, where sulfate may be a substituent on one or more galactose residues; wherein the Globo-H comprises Fucose-alpha2-Gal-beta3-GalNAc-beta3-Gal-alpha-4-Gal-beta-4-Glc; and/or wherein the LNT-2 comprises GlcNAc-beta3-Gal-beta-4-Glc-beta.
9 . The array of claim 1 , wherein the library of glycans further comprises one or more of the following glycans:
Glycan
AGP α-acid glycoprotein
AGPAα-acid glycoprotein glycoformA
AGPBα-acid glycoprotein glycoformB
Ceruloplasmine
Fibrinogen
Transferrin
(Ab4[Fa3]GNb)2#sp1 LeX
(Ab4[Fa3]GNb)3#sp1 LeX
(Ab4GNb)3#sp1 Tri-LacNAc
[3OSO3]Ab#sp2 3SuGal
[3OSO3]Ab3ANa#sp2 3′SuGalβ3GalNAc
[3OSO3]Ab3GNb#sp2 3′SuGalβ3GalNAc
[3OSO3]Ab4[6OSO3]Gb#sp1 3′6DiSuLac
[3OSO3]Ab4[6OSO3]Gb#sp2 3′6DiSuLac
[3OSO3]Ab4Gb#sp2 3′SuLac
[3OSO3]Ab4GNb#sp2 3′SuLacNAc
[4OSO3]Ab4GNb#sp2 4′SuLacNAc
[6OPO3]Ma#sp2 6Pman
[6OSO3]Ab4[6OSO3]Gb#sp2 6′6DiSuLac
[6OSO3]Ab4Gb#sp1 6′SuLac
[6OSO3]Ab4Gb#sp2 6′SuLac
[6OSO3]GNb#sp2 6SuGlcNAc
[GNb3[GNb6]GNb4]ANa#sp2
[NNa3Ab]2GNb#sp2 (Sia)2GlcNAc
3OSO3Ab3[Fa4]GNb#sp2 3′SuLe a
3OSO3Ab4[Fa3]GNb#sp2 3′SuLe X
9NAcNNa#sp2 9NAc-Neu5Ac
9NAcNNa6Ab4GNb#sp2 9NAc-Neu5Ac2,6LacNAc
Aa#sp2 Galα
Aa2Ab#sp2 Galα2Gal
Aa3[Aa4]Ab4GNb#sp2 Galα3[Galα4]LacNAc
Aa3[Fa2]Ab#sp2 Galα3[Fuc]Galβ
Aa3Ab#sp2 Galα3Gal
Aa3Ab4[Fa3]GN#sp2 Galα3Le X
Aa3Ab4Gb#sp1 Galα3Lac
Aa3Ab4GN#sp2 Galα3LacNAc
Aa3Ab4GNb#sp2 Galα3LacNAc
Aa3ANa#sp2 Galα3GalNAc
Aa3ANb#sp2 Galα3GalNAc
Aa4[Fa2]Ab4GNb#sp2 Galα4[Fucα2]LacNAc
Aa4Ab4Gb#sp1 Galα4Lac
Aa4Ab4GNb#sp1 Galα4LacNAc
Aa4Ab4GNb#sp2 Galα4LacNAc
Aa4GNb#sp2 Galα4GlcNAc
Aa6Gb#sp2 Galα6Gal
Ab#sp2 Gal
Ab[NNa6]ANa#sp2 6Sialyl-T
Ab2Ab#sp2 Galβ2Gal
Ab3[Ab4GNb6]ANa#sp2 6LacNAc-Core2
Ab3[Fa4]GNb#sp1 Le a
Ab3[Fa4]GNb#sp2 Le a
Ab3[GNb6]ANa#sp2 Core-2
Ab3[NNa6]GNb4Ab4Gb#sp4 LSTc
Ab3[NNb6]ANa#sp2 β6Sialyl-T
Ab3Ab#sp2 Galβ3Gal
Ab3ANa#sp2 Galβ3GalNAcα
Ab3ANb#sp2 Galβ3GalNAcβ
Ab3ANb4[NNa3]Ab4Gb#sp1 GM1
Ab3ANb4Ab4Gb#sp2 a-sialo-GM1
Ab3GNb#sp1 LeC
Ab3GNb#sp2 LeC
Ab3GNb3Ab4Gb4b#sp4 LNT
Ab4[6OSO3]Gb#sp16SuLac
Ab4[6OSO3]Gb#sp2 6SuLac
Ab4[Fa3]GNb#sp1 LeX
Ab4[Fa3]GNb#sp2 LeX
Ab4ANa3[Fa2]Ab4GNb#sp2
Ab4Gb#sp1 Lac
Ab4Gb#sp2 Lac
Ab4GNb#sp1 LacNAc
Ab4GNb#sp2 LacNAc
Ab4GNb3[Ab4GNb6]Ana#sp2 (LacNAc)2-Core2
Ab4GNb3Ab4[Fa3]GNb3Ab4[Fa3]GNb#sp1 LacNAc-
LeX-LeX
Ab4GNb3Ab4Gb#sp1 LNnT
Ab4GNb3Ab4Gb#sp2 LNnT
Ab4GNb3Ab4GNb#sp1 LacNAc-LacNAc
Ab4GNb3ANa#sp2a 3LacANcα-Core-2
Ab4GNb3ANa#sp2b 3LacNAcβ-Core-2
Ab4GNb6ANa#sp2 6LacANcα-Core-2
Ana#sp2 Tn
Ana3[Fa2]Ab#sp2 A-tri
Ana3Ab#sp2 GalNAcα3Gal
Ana3Ab4GNb#sp2 GalNAcα3LacNAc
Ana3ANb#sp2 GalNAcα3GalNAc
Ana4[Fa2]Ab4GNb#sp2 GalNAcα4[Fucα2]LacNAc
ANb#sp2 GalNAcβ
ANb3[Fa2]Ab#sp2 GalNAcβ[Fucα2]Gal
ANb3Ana#sp2 GAlNAcβ3GalNAc
ANb4GNb#sp1 LacDiNAc
ANb4GNb#sp2 LacDiNAc
Fa#sp2 Fuc
Fa#sp3 Fuc
Fa2Ab#sp2 Fucα2Gal
Fa2Ab3[Fa4]GNb#sp2 Le b
Fa2Ab3Ana#sp2 H-type 3
Fa2Ab3ANb3Aa#sp3 H-type3β3Gal
Fa2Ab3ANb3Aa4Ab4G#sp3 Globo-H
Fa2Ab3ANb4[NNa3]Ab4Gb#sp1 Fucosyl-GM1
Fa2Ab3GNb#sp1 H-type 1
Fa2Ab3GNb#sp2 H type 1
Fa2Ab4[Fa3]GNb#sp1 Le Y
Fa2Ab4[Fa3]GNb#sp2 LeY
Fa2Ab4Gb#sp1 2′Flac
Fa2Ab4GNb#sp1 H-type 2
Fa2Ab4GNb#sp2 H-type 2
Fa2Ab4GNb3Ab4GNb#sp1 H-type-2-LacNAc
Fa2Ab4GNb3Ab4GNb3Ab4GNb#sp1 H-type2-LacNAc-
LacNAc
Fa2GNb#sp2 Fucα2GlcNAc
Fa3GNb#sp2 Fucα3GlcNAc
Fb3GNb#sp2 Fucβ3GlcNAc
Fa2Ab3ANb4[NNa3]Ab4Gb#sp3 Fucosyl-GM1
Ga#sp2 Galα
Ga4Gb#sp2 Galα4Gal
Gb#sp2 Galβ
Gb4Gb#sp2 Galβ4Gal
Gb6Gb#sp2 Galβ6Gal
GNb#sp1 GlcNAc
GNb#sp2 GlcNAc
GNb2Ab3ANa#sp2 GlcNAcβ2-Core-1
GNb3[GNb6]ANa#sp2 GlcNAcβ3[GlcNAcβ6GalNAc
GNb3Ab#sp2 GlcNAcβ3Gal
GNb3Ab3ANa#sp2 GlcNAcβ3-Core1
GNb3Ab4Gb#sp1 LNT-2
GNb3Ab4GNb#sp1 GlcNAcβ3LacNAc
GNb4[GNb6]ANa#sp2 GlcNAcβ4[GlcNAcβ6]GalNAc
GNb4GNb4GNb4b#sp2 Chitotriose
GNb4MDPLys
GNb6ANs#sp2 GlcANcβ6GalNAc
G-ol-amine glucitolamine
GUa#sp2 Glucurinic acidα
GUb#sp2 Glucuronic acidβ
Ka3Ab3GNb#sp1 KDNα2,3-type1
Ka3Ab4GNb#sp1 KDBα2,3-LacNAc
Ma#sp2 Mannose α
Ma2Ma2Ma3Ma#sp3
Ma2Ma3[Ma2Ma6]Ma#sp3
Ma2Ma3Ma#sp3
Ma3[Ma2Ma2Ma6]Ma#sp3
Ma3[Ma6]Ma#sp3 Man-3
Man-5#aa Man5-aminoacid
Man5-9 pool Man5-9-aminoacid
Man-6#aa Man6-aminoacid
Man-7#aa Man7-aminoacid
Man-8#aa Man8-aminoacid
Man-9#aa Man9-aminoacid
Na8Na#sp2 Neu5Acα2,8Neu5Ac
Na8Na8Na#sp2 Neu5Acα2,8Neu5Acα2,5Neu5Ac
NJa#sp2 Neu5Gc
NJa3Ab3[Fa4]GNb#sp1 Neu5GcLe a
NJa3Ab3GbN#sp1 Neu5Gc-type1
NJa3Ab4[Fa3]GNb#sp1 Neu5Gc-LeX
NJa3Ab4Gb#sp1 Neu5Gcα3Lactose
NJa3Ab4GNb#sp1 Neu5Gcα3LacNAc
NJa6Ab4GNb#sp1 Neu5Gcα6LacNAc
NJa6ANa#sp2 Neu5Gc6GalNAc (STn)
NNa#sp2 Neu5Ac
NNa3[6OSO3]Ab4GNb#sp2 3′Sia[6′Su]LacNAc
NNa3[ANb4]Ab4Gb#sp1 GM2
NNa3[ANb4]Ab4GNb#sp1 GM2(NAc)/CT/Sda
NNa3[ANb4]Ab4GNb2#sp1 sp1GM2(NAc)/CT/Sda
NNa3{Ab4[Fa3]GN}3b#sp1 Sia3-TriLeX
NNa3Ab#sp2 Neu5Acα2,3Gal
NNa3Ab3[6OSO3]Ana#sp2 Neu5Acα3[6Su]-T
NNa3Ab3[Fa4]GNb#sp2 SLe a
NNa3Ab3[NNa6]Ana#sp2 Di-Sia-T
NNa3Ab3ANa#sp2 3-Sia-T
NNa3Ab3GNb#sp1 Neu5Acα3Type-1
NNa3Ab3GNb#sp2 Neu5Acα3Type-1
NNa3Ab4[6OSO3]GNb#sp23′Sia[6Su]LacNAc
NNa3Ab4[Fa3][6OSO3]GNb#sp2 6Su-SleX
NNa3Ab4[Fa3]GNb#sp1 SleX
NNa3Ab4[Fa3]GNb#sp2 SleX
NNa3Ab4[Fa3]GNb3Ab#sp2 SleX penta
NNa3Ab4[Fa3]GNb3Ab4GNb#sp1 SleXLacNAc
NNa3Ab4Gb#sp1 3′Sialyllactose
NNa3Ab4Gb#sp2 3′Sialyllactose
NNa3Ab4GNb#sp1 3′SialyllacNAc
NNa3Ab4GNb#sp2 3′SialyllacNAc
NNa3Ab4GNb3Ab4GNb#sp1 3′SialylDiLacNAc
NNa3Ab4GNb3Ab4GNb3Ab4GNb#sp1 3′Sialyl-tri-
LacNAc
NNa3ANa#sp2 Siaα3GalNAc
NNa6Ab#sp2 Siaα6Gal
NNa6Ab4[6OSO3]]GNb#sp2 6′Sial[6Su]LacNAc
NNa6Ab4Gb#sp1 6′Sia-lactose
NNa6Ab4Gb#sp2 6′Sia-lactose
NNa6Ab4GNb#sp1 6′Sia-LacNAc
NNa6Ab4GNb#sp2 6′Sia-LacNAc
NNa6Ab4GNb3Ab4[Fa3]GNb3Ab4[Fa3]GNb#sp1 6Sia-
LacNAc-LeX-LeX
NNa6Ab4GNb3Ab4GNb#sp1 6SiaLacNAc-LacNAc
NNa6ANa#sp2 6SiaβGalNAc
NNa8NNa3[ANb4]Ab4Gb#sp1 GD2
NNa8NNa3Ab4Gb#sp1 GD3
NNa8NNa8NNa3[ANb4]Ab4Gb#sp1 GT2
NNa8NNa8NNa3Ab4Gb#sp1 GT3
NNAa3[NNa6]Ana#sp2 (Sia)2-Tn
NNb#sp2 Siaβ
NNb6Ab4GNb#sp2 6′SiaβLacNAc
NNb6ANa#sp2 βSTn
OS-11#sp2 6′sialLacNAc-biantenary glycan
Ra#sp2 Rhamnose
Abbreviations employed:
Sp1 = OCH2CH2NH2;
Sp2 = Sp3 = OCH2CH2CH2NH2
A = Gal; AN = GalNAc; G = Glc; GN = GlcNAc;
F = Fucose; NN; Neu5Ac (sialic acid);
NJ = Neu5Gc (N-glycolylsialic acid); a = α; b = β;
Su = sulfo; T = Galβ3GalNAc (T-antigen);
Tn = GalNAc (Tn-antigen).
10 . The array of claim 1 comprising about 10 to about 200 glycans.
11 . A breast cancer epitope selected from the group consisting of ceruloplasmin, Neu5Gc(2-6)GalNAc, GM1, Sulfo-T, Globo-H, LNT-2, Tri-LacNAc, LacNAc-LeX-LeX, LacNAc-LacNAc, H-type-2-LacNAc, H-type2-LacNAc-LacNAc, GlcNAcβ3LacNAc, SLeXLacNAc, 3′SialylDiLacNAc, 3′Sialyl-tri-LacNAc, 6Sia-LacNAc-LeX-LeX and 6SiaLacNAc-LacNAc glycans.
12 . A composition comprising a carrier and an effective amount of at least one glycan molecule that binds antibodies associated with neoplasia of patients with benign, pre-malignant or malignant breast tumors.
13 . The composition of claim 12 , wherein the glycan molecule is selected from the group consisting of ceruloplasmin, Neu5Gc(2-6)GalNAc, GM1, Sulfo-T, Globo-H, sialylated Tn (Neu5Ac-alpha6-GalNAc-alpha), LNT-2, Tri-LacNAc, LacNAc-LeX-LeX, LacNAc-LacNAc, H-type-2-LacNAc, H-type2-LacNAc-LacNAc, GlcNAcβ3LacNAc, SLeXLacNAc, 3′SialylDiLacNAc, 3′Sialyl-tri-LacNAc, 6Sia-LacNAc-LeX-LeX and 6SiaLacNAc-LacNAc glycans.
14 . The composition of claim 13 , wherein the GM1 is Gal-beta3-GalNAc-beta-4-[Neu5Ac-alpha3]-Gal-beta-4-Glc-beta; wherein the Sulfo-T comprises a T-antigen with sulfate residues; wherein the Sulfo-T comprises Galβ3GalNAc, wherein sulfate can be present on one or more of the Sulfo-T galactose residues; wherein the Globo-H comprises Fucose-alpha2-Gal-beta3-GalNAc-beta3-Gal-alpha-4-Gal-beta-4-Glc; and/or wherein the LNT-2 comprises GlcNAc-beta3-Gal-beta-4-Glc-beta.
15 . The composition of claim 13 , which has at least two glycan molecules.
16 . The composition of claim 13 , which is formulated for immunization of a mammal.
17 . The composition of claim 13 , which is formulated for local administration to the breast.
18 . The composition of claim 13 , which is formulated as a food supplement.
19 . A method of detecting breast cancer comprising contacting the array of claim 1 with a test sample obtained from a patient and observing whether antibodies in the test sample bind to at least one glycan molecule in the array that has previously determined to bind antibodies associated with neoplasia in patients with benign, pre-malignant or malignant breast tumors.
20 . The method of claim 19 , wherein the test sample is a blood sample, a serum sample, a plasma sample, a urine sample, a breast milk sample, an ascites fluid sample or a tissue sample.
21 . The method of claim 19 , wherein the glycan molecule is selected from the group consisting of ceruloplasmin, Neu5Gc(2-6)GalNAc, GM1, Sulfo-T, Globo-H, sialylated Tn (Neu5Ac-alpha6-GalNAc-alpha), LNT-2, Tri-LacNAc, LacNAc-LeX-LeX, LacNAc-LacNAc, H-type-2-LacNAc, H-type2-LacNAc-LacNAc, GlcNAcβ3LacNAc, SLeXLacNAc, 3′SialylDiLacNAc, 3′Sialyl-tri-LacNAc, 6Sia-LacNAc-LeX-LeX and 6SiaLacNAc-LacNAc glycans.
22 . The method of claim 21 , wherein the GM1 is Gal-beta3-GalNAc-beta-4-[Neu5Ac-alpha3]-Gal-beta-4-Glc-beta; wherein the Sulfo-T comprises a T-antigen with sulfate residues; wherein the Sulfo-T comprises Galβ3GalNAc; wherein the Globo-H comprises Fucose-alpha2-Gal-beta3-GalNAc-beta3-Gal-alpha-4-Gal-beta-4-Glc; and/or wherein the LNT-2 comprises GlcNAc-beta3-Gal-beta-4-Glc-beta.
23 . The method of claim 19 , which further comprises observing whether antibodies in a control sample bind to at least one glycan molecule that binds antibodies associated with neoplasia in patients with benign, pre-malignant or malignant breast tumors; wherein the control sample is from a patient that does not have breast cancer.
24 . A method of detecting antibodies that bind breast cancer-related glycan epitopes comprising contacting a serum sample with the array of glycans of claim 1 and observing whether one or more glycans are bound by antibodies.
25 . A method of treating or preventing breast cancer in a mammal that comprises administering to the mammal the composition of claim 12 .
26 . The method of claim 25 , wherein the at least one glycan molecule is selected from the group consisting of ceruloplasmin, Neu5Gc(2-6)GalNAc, GM1, Sulfo-T, Globo-H, sialylated Tn (Neu5Ac-alpha6-GalNAc-alpha), LNT-2, Tri-LacNAc, LacNAc-LeX-LeX, LacNAc-LacNAc, H-type-2-LacNAc, H-type2-LacNAc-LacNAc, GlcNAcβ3LacNAc, SLeXLacNAc, 3′SialylDiLacNAc, 3′Sialyl-tri-LacNAc, 6Sia-LacNAc-LeX-LeX and 6SiaLacNAc-LacNAc glycans.
27 . The method of claim 26 , wherein the GM1 is Gal-beta3-GalNAc-beta-4-[Neu5Ac-alpha3]-Gal-beta-4-Glc-beta; wherein the Sulfo-T comprises a T-antigen with sulfate residues; wherein the Sulfo-T comprises Galβ3GalNAc; wherein the Globo-H comprises Fucose-alpha2-Gal-beta3-GalNAc-beta3-Gal-alpha-4-Gal-beta-4-Glc; and/or wherein the LNT-2 comprises GlcNAc-beta3-Gal-beta-4-Glc-beta.
28 . The method of claim 25 , wherein the composition has at least two glycan molecules.
29 . The method of claim 25 , wherein the composition is formulated for immunization of a mammal.
30 . The method of claim 25 , wherein the composition is locally administered to the mammal's breast.
31 . The method of claim 25 , wherein the composition is administered as a food supplement.
32 . An isolated antibody that can bind the breast cancer epitope of claim 11 .
33 . The isolated antibody of claim 32 , wherein the antibody can bind a glycan molecule selected from the group consisting of Tri-LacNAc, LacNAc-LeX-LeX, LacNAc-LacNAc, H-type-2-LacNAc, H-type2-LacNAc-LacNAc, GlcNAcβ3LacNAc, SLeXLacNAc, 3′SialylDiLacNAc, 3′Sialyl-tri-LacNAc, 6Sia-LacNAc-LeX-LeX and 6SiaLacNAc-LacNAc.
34 . A method of treating or preventing breast cancer in a mammal that comprises administering to the mammal a composition comprising an effective amount of the antibody of claim 32.Join the waitlist — get patent alerts
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